PMID- 11410238
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190910
IS  - 0162-0134 (Print)
IS  - 0162-0134 (Linking)
VI  - 85
IP  - 2-3
DP  - 2001 Jun
TI  - Amelioration of insulin resistance in diabetic ob/ob mice by a new type of orally 
      active insulin-mimetic vanadyl complex: 
      bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) with VO(S(2)O(2)) coordination mode.
PG  - 179-86
AB  - Recently, we have shown that a newly synthesized vanadyl complex, 
      bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), VO(opt)(2), is a potent orally 
      active insulin-mimetic in treating streptozotocin-induced diabetes in rats, with 
      long-term action. In the present study, the anti-diabetic effect of VO(opt)(2) 
      and its mechanism in ob/ob mice, an obese non-insulin-dependent diabetes mellitus 
      (NIDDM) animal model, was investigated. In ob/ob mice, 15-day oral treatment with 
      VO(opt)(2) resulted in a dose-dependent decrease in the levels of glucose, 
      insulin and triglyceride in blood. VO(opt)(2) was also effective in ameliorating 
      impaired glucose tolerance in ob/ob mice, when an oral glucose tolerance test was 
      performed after treatment with VO(opt)(2). Tumor necrosis factor-alpha 
      (TNF-alpha) is a key component of obesity-diabetes link, we therefore examined 
      the attenuating effect of VO(opt)(2) on impaired insulin signal transduction 
      induced by TNF-alpha. Elevated expression of TNF-alpha was observed in the 
      epididymal and subcutaneous fat tissues of ob/ob mice. Incubation of 3T3-L1, 
      mouse adipocytes, with TNF-alpha reduced the phosphorylation of insulin receptor 
      substrate-1 (IRS-1), whereas VO(opt)(2) treatment resulted in an enhancement of 
      IRS-1 phosphorylation, irrespective of the presence or absence of TNF-alpha. 
      Overall, the present study demonstrates that VO(opt)(2) exerts an anti-diabetic 
      effect in ob/ob mice by ameliorating impaired glucose tolerance, and furthermore, 
      attenuates the TNF-alpha-induced decrease in IRS-1 phosphorylation in adipocytes. 
      These results suggest that the anti-diabetic action of VO(opt)(2) is derived from 
      an attenuation of a TNF-alpha induced impaired insulin signal transduction via 
      inhibition of protein tyrosine phosphatase, providing a potential clinical 
      utility for VO(opt)(2) in the treatment of NIDDM.
FAU - Takeshita, S
AU  - Takeshita S
AD  - Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 
      2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
FAU - Kawamura, I
AU  - Kawamura I
FAU - Yasuno, T
AU  - Yasuno T
FAU - Kimura, C
AU  - Kimura C
FAU - Yamamoto, T
AU  - Yamamoto T
FAU - Seki, J
AU  - Seki J
FAU - Tamura, A
AU  - Tamura A
FAU - Sakurai, H
AU  - Sakurai H
FAU - Goto, T
AU  - Goto T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Inorg Biochem
JT  - Journal of inorganic biochemistry
JID - 7905788
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Leptin)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Phosphoproteins)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bis(1-oxy-2-pyridinethiolato)oxovanadium(IV))
RN  - 20644-97-7 (oxovanadium IV)
RN  - 3WHH0066W5 (Vanadates)
SB  - IM
MH  - 3T3 Cells
MH  - Adipose Tissue/drug effects/metabolism
MH  - Administration, Oral
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Insulin/blood
MH  - Insulin Receptor Substrate Proteins
MH  - *Insulin Resistance/genetics
MH  - Kinetics
MH  - Leptin/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Organometallic Compounds/administration & dosage/*pharmacology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Triglycerides/blood
MH  - Tumor Necrosis Factor-alpha/drug effects/metabolism
MH  - Vanadates/administration & dosage/*pharmacology
EDAT- 2001/06/19 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/06/19 10:00
PHST- 2001/06/19 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/06/19 10:00 [entrez]
AID - S0162-0134(01)00192-1 [pii]
AID - 10.1016/s0162-0134(01)00192-1 [doi]
PST - ppublish
SO  - J Inorg Biochem. 2001 Jun;85(2-3):179-86. doi: 10.1016/s0162-0134(01)00192-1.